Transcriptional and post-transcriptional effects of nerve growth factor on expression of the three neurofilament subunits in PC-12 cells.

Nerve growth factor (NGF) is known to increase the levels of neurofilament proteins in PC-12 pheochromocytoma cells. In this report, we show that the three neurofilament subunits, NF-L, NF-M, and NF-H, are not induced coordinately. NF-H accumulated only after longer term NGF treatment than required for NF-L and NF-M. While NGF treatment resulted in 12- and 14-fold increases in NF-L and NF-M mRNA levels, respectively, over a 14-day period, no increase in the level of NF-H mRNA was observed. This indicated that in PC-12 cells, control of NF-H expression by NGF may occur at the post-transcriptional level. NGF appeared to have no effect on the stability of NF-L mRNA, although it increased the stability of NF-M mRNA relative to that in control PC-12 cells. Analysis of the effect of NGF on the transcription of neurofilament genes showed 4- and 5-fold increases in the rates of NF-L and NF-M gene transcription, respectively, and no increase in the rate of NF-H gene transcription. Taken together these results demonstrate that NGF stimulates the expression of individual neurofilament subunits at the transcriptional and/or post-transcriptional levels.